Equis ISSN 2398-2977

Toxicity: pyrrolizidine alkaloid

Synonym(s): Ragwort toxicosis, Oral habout disease, Dunsiekte, Winton disease, Pictou disease, Suilkut disease, Schweinsberger disease

Contributor(s): Debbie Deem Morris, Nicola Menzies-Gow, Wilson Rumbeiha, Prof Alan Seawright

Introduction

  • Pyrrolizidine alkaloids are toxins which mainly cause hepatotoxicity and liver failure but may also cause respiratory disease and renal damage depending on the plants involved.
  • Cause: pyrrolizidine alkaloids are produced by 3 main plant families:
    • Asteraceae (Senecio spp, tansy ragwort).
    • Tobaceae (Crotalaria spp, rattlebox).
    • Boraginaceae (HeliotropumAmsinckiaTrichodesma and Echium spp).
  • Signs: anorexia, weight loss, ventral edema, depression, icterus +/- signs of hepatic encephalopathy, eg apparent blindness, circling, head-pressing; respiratory distress.
  • Diagnosis: liver function tests, hepatic biopsy, liver enzymes, alkaloids in liver, necropsy.
  • Treatment: no effective specific treatment.
  • Prognosis: poor if recurrent or severe.
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Pathogenesis

Etiology

  • Pyrrolizidine alkaloids produced by plants.
  • Ragwort (Senecio jacobea) Ragwort: floweringRagwort: Spring - contains 8 alkaloids, including retrorsine.
  • Heliotrope contains several alkaloids, including lasiocarpine and heliotrine.
  • Crotalaria spp contain mainly monocrotaline, some also contain fulvine and crispatine.

Predisposing factors

General

  • Plants containing pyrrolizidine alkaloids are usually, but not always, unpalatable and mostly ignored.
  • May be consumed when there is little alternative feed.
  • Dead ragwort and other pyrrolizidine alkaloid plants, eg in hay, are more palatable.
  • Repeated ingestion of small amounts over several seasons may → disease - cumulative effect.

Pathophysiology

  • Pyrrolizidine alkaloids have primary toxic effect on hepatic parenchyma and secondary effects on hepatic veins, pulmonary tissues and other extrahepatic tissues such as the lungs, kidneys and heart.
  • Clinical signs occur once liver damage has progressed sufficiently to compromise liver function.
  • Alkaloids → primary toxic effect on liver parenchyma → megalocytosis → necrosis and inhibition of cell division.
  • Reactive alkaloids crosslink DNA, impair cell division and may affect protein synthesis.
  • Can interfere with copper excretion.
  • Secondary toxic effect on centrilobular and hepatic veins → endothelial damage and perivascular fibrosis → vascular occlusion.
  • Apparent sudden onset, often weeks after ingestion has stopped → hepatic encephalopathy Liver: hepatoencephalopathy.

Timecourse

  • Usually chronic.
  • Liver damage may accumulate over several years.
  • Onset of clinical signs may occur several weeks to months after ingestion of plant has stopped.

Epidemiology

  • Plants are not usually palatable, therefore ignored unless food is scarce.
  • Dead plants, eg in hay, are readily eaten.
  • Toxicity is cumulative; liver damage may occur over several seasons.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Bothia C J et al (2012) Crotalariosis equorum ("jaagsiekte") in horses in southern Mozambique, a rare form of pyrrolizidine alkaloid poisoning. J Vet Diag Invest 24 (6), 1099-1104 PubMed.
  • Creeper J H et al (1999) Pyrrolizidine alkaloid poisoning of horses grazing a native heliotrope (Heliotropium ovalifolium). Aust Vet J 77 (6), 401-402 PubMed.
  • Curran J M, Sutherland R J & Peet R L (1996) A screening test for subclinical liver disease in horses affected by pyrrolizidine alkaloid toxicosis. Aust Vet J 74 (3), 236-240 PubMed.
  • Winter H et al (1993) Pyrrolizidine alkaloid poisoning of yaks - diagnosis of pyrrolizidine alkaloid exposure by the demostration of sulphur-conjugated pyrrolic metabolites of the alkaloid in circulating haemoglobin. Aust Vet J 70 (8), 312-313 PubMed.
  • Pearson E G (1991) Liver failure attributable to pyrrolizidine alkaloid toxicosis and associated with inspiratory dyspnea in ponies - 3 cases. JAVMA 198 (9), 1651-1654 PubMed.


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